Menopausal Vulvovaginitis
William J. Ledger, Steven S. Witkin in Vulvovaginal Infections, 2017
In this diagnostic evaluation, it is also important to get a detailed medical history and current use of drugs by these patients. Women with a history of breast or endometrial cancer will not ordinarily be candidates for systemic or local estrogens. Some liver illnesses, such as cirrhosis from a chronic hepatitis B or C infection, can preclude the use of oral estrogens as a treatment option. Tamoxifen citrate can cause vaginal symptomatology for patients under care for breast cancer. Any history of allergy is important. If local estrogens have been used, inquiries need to be made to see if the patient has had any adverse reactions to them. They can cause severe vaginal or vulvar burning after the application of an estrogen cream that contains propylene glycol as a preservative. In these situations, the vaginal estrogen tablet that has no propylene glycol would seem to be an ideal choice, but menopausal women with reduced vaginal secretions can develop vaginal or vulvar irritation within a day or two of inserting the vaginal estrogen tablet from the gritty discharge of an incompletely dissolved tablet.
Breast Cancer
Mary J. Marian, Gerard E. Mullin in Integrating Nutrition Into Practice, 2017
Adjuvant endocrine therapy is instituted for breast cancers that are estrogen or progesterone receptor-positive (ER-positive and PR-positive).27 The two SERMs used for treatment of breast cancer, tamoxifen and raloxifene (Evista®), compete with estrogen for receptor sites in target tissues such as the breast. Tamoxifen is used for adjuvant treatment for premenopausal breast cancer. This drug exerts estrogen-like activity on the skeletal and cardiovascular systems, reducing bone loss and improving lipid levels. Side effects of tamoxifen include hot flashes, night sweats, and vaginal dryness. Serious adverse effects include an increased risk of cataracts, endometrial cancer, and pulmonary embolism. The U.S. Food and Drug Administration approved raloxifene for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. The STAR trial that compared Tamoxifen and Raloxifen suggested near equal efficacy supporting a 50% reduction in risk, but with less thrombotic events in the Raloxifen group.28
Basis for the Use of Drug and Hormone Combinations in the Treatment of Endocrine-Related Cancer
Nicholas Bruchovsky, James H. Goldie in Drug and Hormone Resistance in Neoplasia, 2019
The major thrust of curative therapy falls upon the early postoperative period and excludes the use of intermittent therapy with a hormonal agent. The latter is reserved for patients whose treatment program is likely to span a long interval of time; it is advocated for several reasons.150 First, the induction of rebound regression by a withdrawal effect, if timed to correspond with effective chemotherapy, may augment the results of treatment. Second, hormonal resistance may be delayed or avoided by interspersing treatment and rest periods. For example, nine months of therapy with tamoxifen might be followed by a break of three months before tamoxifen is resumed. Third, by successively stimulating cells to enter the proliferative cycle, sensitivity to chemotherapeutic agents may be repetitively augmented or restored. Fourth, avoidance of long periods of hormone deprivation or replacement therapy may retard progression and maintain hormone sensitivity. Lastly, the side effects attributable to hormone are reduced.
Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats
Published in Toxicology Mechanisms and Methods, 2020
Ademola C. Famurewa, Chima A. Ekeleme-Egedigwe, Ebuka E. David, Chinedum O. Eleazu, Abiola M. Folawiyo, Nwogo A. Obasi
Tamoxifen (TAM) is a nonsteroidal antiestrogen agent used to treat hormone-dependent breast cancer (Suddek 2014a). TAM citrate was approved by the Food and Drug Administration in 1977 for the treatment of women with advanced breast cancer (Osborne 1998). Recently, it is applied in the chemoprevention strategies for healthy women at high risk of breast cancer development (Suddek 2014a). The anticancer mechanism of TAM is associated with its anti-estrogenic activity mediated by estrogen receptor antagonistic property (Albukhari et al. 2009). This property inhibits the expression of estrogen-regulated genes and exerts arrest of G1 phase in cancer cell cycle (Osborne 1998). Despite the widespread therapeutic and emerging prophylactic use of TAM, the worrying adverse effect is particularly liver toxicity (Parvez et al. 2006; Suddek 2014b). TAM-induced hepatotoxicity is a considerable complication in female patients undergoing TAM chemotherapy. At high doses, TAM is a potent hepatocarcinogen in rodents and an inducer of hepatosteatosis, cirrhosis, and acute pancreatitis in humans (Parvez et al. 2006; Albukhari et al. 2009; Singh et al. 2016).
Future perspectives for cryptococcosis treatment
Published in Expert Opinion on Therapeutic Patents, 2018
Juliana Santos-Gandelman, Márcio Lourenço Rodrigues, Alice Machado Silva
Though interesting and novel molecules were identified in this patent landscape, we consider the development of these compounds unlikely unless they also target other indications (given the previously mentioned market failure for cryptococcosis). Repurposing is most likely the most promising strategy for establishing novel anti-cryptococcal agents. Drug repurposing is faster and much cheaper than developing novel molecules of pharmacological potential [81,82]. Several studies are evaluating possible candidates for drug repurposing for cryptococcosis treatment [83–88]. Tamoxifen, an estrogen receptor antagonist used primarily to treat breast cancer, is one of these compounds. Tamoxifen in combination with AmpB and fluconazole is about to enter phase II clinical trials for the treatment of cryptococcal meningitis (clinical.trial.gov identifier NCT03112031). Indeed, patents demonstrating tamoxifen’s activity against Cryptococcus spp. were retrieved in our search. However, they were not summarized due to the absence of in vivo experimental evidence of such activity.
Addressing the problem of overtreatment in breast cancer
Published in Expert Review of Anticancer Therapy, 2022
Another area of concern regarding overtreatment in DCIS is the use of endocrine therapy. Two randomized controlled trials have demonstrated the benefit of tamoxifen in reducing both ipsilateral and contralateral breast events following excision of DCIS. After a median follow-up of 14.6 years, the NSABP B-24 trial demonstrated a significant reduction in the rate of invasive breast cancer (no tamoxifen 19%, tamoxifen 12%) but not in the rate of DCIS (12% versus 9%, p = 0.12) [84]. The UK/ANZ DCIS trial demonstrated a reduction in 10-year risk of recurrent ipsilateral DCIS (no tamoxifen 12.1%, tamoxifen 8.6%) and contralateral tumors (4.2% versus 1.9%), but not of ipsilateral invasive disease (6.9% versus 6.8%) [85]. No difference in survival was seen in either trial. Tamoxifen and other anti-estrogen therapies have side effects, including vasomotor symptoms, thromboembolic events, and endometrial cancer. For many women, these side effects outweigh the small absolute reduction in new invasive events. Uptake of endocrine therapy for DCIS is relatively low, ranging from 21% to 47% [86]. Endocrine therapy should be discussed as an option for those who wish to minimize the risk of future breast cancer events and have a favorable risk-benefit ratio for treatment (premenopausal, 2 breasts at risk), but should not be considered a mandatory part of DCIS management.
Related Knowledge Centers
- Selective Estrogen Receptor Modulator
- Uterine Cancer
- Pulmonary Embolism
- Stroke
- Breast Cancer
- Cancer
- McCune–Albright Syndrome
- Oral Administration
- Irregular Menstruation
- Hot Flash